PROJECT SUMMARY: Keratoconus and related corneal ectasias are a major cause of vision loss in young adults, the primary concern during refractive surgery screening to treat myopia, and the leading indication for corneal transplantation in the US. These conditions are known to be triggered by the disruption of the mechanical balance between corneal strength and intraocular outward pressure, which can occur naturally in ectatic disorders or can be triggered by refractive surgery procedures. While it is critical to identify weakened (ectatic) corneas at their earliest time point, current imaging techniques are unable to do that, as they only assess corneal morphology (shape) and not corneal biomechanics. This leaves doctors and patients with limited information when diagnosing keratoconus, or when planning surgeries. To overcome current corneal screening limitations, we have developed an optical technology, Brillouin microscopy, which can measure corneal stiffness at high 3- dimensional resolution without contacting or perturbing the eye. The overall goal of this research program is to improve diagnosis and management of corneal ectatic disorders and to improve the safety and outcome of refractive surgery procedures by introducing novel biomechanical profiling of the cornea. Our central hypothesis is that spatially localized changes in mechanical properties of the cornea are critical drivers of the morphological behavior observed in the clinic. This hypothesis is driven by strong preliminary data showing remarkable region dependent changes in ectatic corneas in vivo. The proposed research will pursue three specific aims: 1) Validate Brillouin measurements for mechanical evaluation of the cornea; 2) Characterize focal Brillouin modulus changes in subclinical keratoconus; 3) Determine the mechanical impact of refractive surgery and cross-linking procedures on the cornea. The research is significant because elasticity-based metrics will enable early identification of corneal ectasia patients when treatments are maximally beneficial, proper screening of individuals at risk of developing post-operative ectasia that might otherwise undergo LASIK, and objective assessment of the mechanical degradation involved with refractive procedures. Ultimately, the knowledge gained from this research is likely to lead to the development of individualized refractive surgery and cross-linking treatment plans based on the patient's underlying biomechanical status.